Early-onset familial HLH due to PRF1 mutation: diagnostic and therapeutic challenges in a resource-limited setting

Familial haemophagocytic lymphohistiocytosis (FHL) is a rare, autosomal recessive immune dysregulation disorder characterised by uncontrolled T-cell and macrophage activation, leading to life-threatening cytokine storm and multi-organ involvement. FLH is rare, with an incidence of 0.12 per 100 000 live births. It usually presents in infancy, but its onset in the newborn period is especially uncommon. Mutations in genes such as PRF1, UNC13D, STX11 and STXBP2 define its subtypes. Diagnostic challenges are common in resource-limited settings due to non-specific presentation and limited access to specialised testing. We report a case of FHL2 caused by a PRF1 mutation in a young infant who presented in the late neonatal period with progressive hepatosplenomegaly, cytopaenias and systemic inflammatory features. This case underscores the importance of early recognition, prompt immunological and genetic evaluation and initiation of haemophagocytic lymphohistiocytosis-directed therapy. It also highlights the feasibility of advanced treatments like haematopoietic stem cell transplantation in low-to-middle-income countries and contributes to the limited genotypic data on FHL in the Indian population.